Drawing Out the Facts

The STEM Chicksmas Day Eight: Cell Signaling

For the 12 Days of “The STEM Chicksmas” we’re highlighting 12 scientists who have contributed something innovative and exciting to their field. It is the season of giving, and these brilliant minds have given incredible gifts to the scientific community! This year we’re looking at 12 Nobel Prize winners from the past 15 years in the fields of Physics, Chemistry, and Physiology or Medicine.

The 2000 Nobel Laureates in Medicine Arvid Carlsson, Paul Greengard, and Eric Kandel all made significant discoveries concerning signal transductions in the nervous system. “Signal transduction” is the process by which a stimulus outside the cell triggers a biochemical response inside the cell. The signaling molecule activates a receptor located on the cell. When this happens in the nervous system, for example in the brain, this process is referred to as synaptic- or neurotransmission. The cells in the nervous system, called neurons, oftentimes do not come into physical contact with each other. Instead they transmit information over a small gap, called the synapse, either chemically or electrically. Chemical transmission is most prevalent in our bodies. One neuron will release neurotransmitters, which are chemical messengers that then bind to a receptor in the second neuron, activating it and eliciting a response. In the nervous system, these responses range from being able to move to being able to think to regulating all of your bodily responses. Understanding signal transduction in the nervous system and better understanding the nervous system in general brings us one step closer to being able to develop better medicine and therapeutic treatments.

Carlsson’s discovery had to do with dopamine’s important role in the brain. Many researchers previously thought that dopamine was a precursor to another type of neurotransmitter, noradrenaline (also known as norepinephrine), rather than being a neurotransmitter itself. However, Carlsson developed a selective test to locate dopamine, and he discovered that dopamine is actually localized in places where noradrenaline is not. To test what dopamine’s role might be, he injected animals with a cocktail of chemicals that froze neurotransmitter activity and consequently their physical movement. When injected with L-dopa, a chemical that converts to dopamine in the body, their movement miraculously returned! Carlsson’s discovery that dopamine plays a role in regulating motor skills is especially important because it led to a greater understanding of Parkinson’s disease, specifically Parkinson’s patients have a shortage of dopamine in a specific area of their brain. To this day, L-dopa is used as a treatment for Parkinson’s to regulate patients’ motor skills. Carlsson’s discovery was also vital for understanding and developing antipsychotics and antidepressives.

Greengard built off of Carlsson’s work. He investigated the mechanism by which neurotransmitters actually work—that is, what happens on the chemical level. He discovered that neurotransmitters like dopamine and serotonin work via slow synaptic transmission, where the change in the neuron may last anywhere from a few seconds to a few hours. This is important for mood, for example, whereas fast synaptic transmission regulates things like speech and actions. He found that this slow synaptic transmission is a mechanism that begins a chemical chain reaction. For instance, dopamine binds with a target receptor on a neuron, which causes the release of a second messenger molecule, which switches on a host of proteins quickly in a cascade reaction through a process called phosphorylation. In phosphorylation, a phosphate group (a group with phosphorous and oxygen) binds to a protein in such a way that it changes its function. One function it changes is the excitability of certain neurons. Excitability refers to the electrical impulse necessary to transfer information synaptically. When the excitability is changed, the neuron transfers information differently. This is important because it led to better understanding of how certain drugs work.

Kandel was interested in memory. He took an animal with a fairly simple nervous system, the sea slug, and applied to the nerve cells. He found that applying certain stimuli increased the protective reflex of the sea slug. Weak stimuli affected short term memory by changing the nerve channels locally. Essentially, phosphorylation and changes in the ion channels of the first cell caused it to release more neurotransmitter into the synaptic space. Therefore, as neurotransmitter levels were increased, the stimulus was increased. Stronger stimuli, on the other hand, changed the production of certain proteins in the synapse. This increased the size of the synapse (the gap between two neurons), which led to an increased synaptic function over the long term—i.e. long term memory! Kandel’s discovery led to an important insight into human memory: it is based in the synapses. We don’t yet understand memory, but Kandel has pointed us in the right direction.

Through the work of these three researchers, medicine has been improved, our understanding of how drugs work and thus our development of new drugs has increased, and we have been set on the path towards understanding complex memory in humans.